Efficient synthesis of an (aminooxy) acetylated-somatostatin derivative using (aminooxy)acetic acid as a ‘carbonyl capture’ reagent

Authors

  • Gábor Mezö,

    Corresponding author
    1. Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary
    • Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, 1117 Budapest, Pázmány P. stny. 1/A, Hungary.
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  • Ildikó Szabó,

    1. Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary
    2. Institute of Chemistry, Eötvös Loránd University, 1117 Budapest, Hungary
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  • István Kertész,

    1. Department of Nuclear Medicine, Medical and Health Science Center, University of Debrecen, 4032 Debrecen, Hungary
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  • Rózsa Hegedüs,

    1. Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary
    2. Institute of Chemistry, Eötvös Loránd University, 1117 Budapest, Hungary
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  • Erika Orbán,

    1. Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary
    2. Institute of Chemistry, Eötvös Loránd University, 1117 Budapest, Hungary
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  • Ulrike Leurs,

    1. Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany
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  • Szilvia Bösze,

    1. Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary
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  • Gábor Halmos,

    1. Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary
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  • Marilena Manea

    Corresponding author
    1. Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany
    2. Zukunftskolleg, University of Konstanz, 78457 Konstanz, Germany
    • University of Konstanz, Zukunftskolleg and Department of Chemistry, Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, Universitätsstrasse 10, 78457 Konstanz, Germany.
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Abstract

Owing to the high chemoselectivity between an aminooxy function and a carbonyl group, oxime ligation is one of the most preferred procedures for the preparation of peptide conjugates. However, the sensitivity of (aminooxy)acetylated peptides to ketones and aldehydes makes their synthesis and storage difficult. In our study, we established the efficient synthesis of an (aminooxy)acetylated-somatostatin derivative in the presence of free (aminooxy)acetic acid, which was used as a ‘carbonyl capture’ reagent in the final cleavage step. This (aminooxy)acetylated compound was further used for the chemoselective ligation (oxime bond formation) with daunorubicin and 4-fluorobenzaldehyde leading to the formation of conjugates with potential applications in targeted cancer chemotherapy and positron emission tomography. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.

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